ABSTRACT
The narrow therapeutic index, non-linear pharmacokinetics and unpredictable absorption require regular therapeutic monitoring of phenytoin. The influence of genetic differences, sex,age and race on the phenytoin plasma levels and its metabolites is well recognized. This study is aimed at evaluating phenytoin plasma drug concentration and its relationship with clinicalrespone, persistent seizures and toxicity in different gender and various age group of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of phenytoin in various sub-groups of epileptic patients for enhancing the safety. efficacy and minimizing the toxicity of phenytoin. A total of 48 plasma samples of epileptic patients for measuring the olasma phenytoin concentration were received. Only patients displaying persistent seizures or suspected adverse effects were requested for drug monitoring. All these samples were analyzed for therapeutic drug monitoring with Enzyme-multiplied immunoassay technique. Suprisingly, it was found that majorities [85.5%] of samples were out of the reference range, of which 69% of samples were in sub-therapeutic levels and 16.5% of samples were above therapeutic levels. Only 14.5% of all samples had phenytoin levels in the therapeutic range. The difference in plasma concentration of phenytoin was notably altered in gender and various age groups. Careful attention must be applied to specific gender and particular age group on an individual basis in the interpretation of plasma concentration results, in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can effect the phenytoin plasma concentration. Through these results, it can be concluded that a good correlation exists between phenytoin plasma concentration and clinical response. Therefore, regular therapeutic monitoring of phenytoin and screening of HLA-A, B,C and DRB1 genotypes before prescribing phenytoin in epileptic patients is essentially required to achieve maximum clinical response and prevent the serious toxicity
ABSTRACT
The unpredictable and unfavorable connection of dose and plasma concentration of valproic acis supports the nescessity to regularly measure its plasma concentration. The present study is drug monitoring of valproic acid and comparative evaluation of therapeutic monitoring results of valproic acid for assessment of clinical response, safety and toxicity in different age and gender groups of Chinese epileptic patients. This knowledge will help the clinicians in adjusting the drug dosages of valproic acid in various sub-groups of epileptic patients for enhancing the safety and minimizing the toxicity of valproic acid. A total of 206 plasma samples [126 males and 80 females] of epileptic patients using valproic acid were requested for therapeutic drug monitoring by neurology department of Qilu Hospital. It was found that 29% of the total samples were found in sub-therapeutic levels. 13% of the samples had toxic levels and 58% of all samples had valproic acid levels in therapeutic range. The difference in plasma concentration of valproiv acid is notably altered in gender and various age groups. However, this requires further investigation. Despite the majority of samples in the therapeutic range, there was an unfavorable clinical response. The outcomes of the current research work exposed that there was a poor correlation between the plasma concentration and clinical response. Careful attention must be applied to specific gender and particular age group on an individual basis in the interpretation of plasma concentration results, in order to facilitate the modification of doses and develop the best approach in treatment and to obtain the desired clinical response because multiple factors can effect the valproic acid plasma concentration. Through these results, it can be concluded that poor correlation exists between valproic acid plasma concentration and clinical response